Provide new ideas for the treatment of genetic eye diseases

Recently, Xu Hui, a research group of iHuman Institute/Life Science and Technology College of Shanghai University of Science and Technology, successfully analyzed the three-dimensional fine structure of the first source of frizzled receptor (Frizzled-4) and published it in the world's leading academic journal Nature. The author of the paper, Xu Fei, a researcher at the iHuman Institute of Shanghai University of Science and Technology, and assistant professor of the School of Life Science and Technology, said in an interview with this reporter that he was very excited to be able to grab the first analysis of Frizzled-4 structure before other international counterparts. The breakthrough, this breakthrough may have a new "strategic map" for the treatment of a genetic eye disease in a newborn.

Challenge emerging research areas from scratch

Our eyes can see, the nose can smell, and the tongue can taste. It is because there are many G protein-coupled receptors (hereinafter referred to as "GPCRs") distributed on the surface of human cells. Its function is equivalent to the "signal soldiers" of cells, responsible for cells. Information exchange between. Once it is out of tune, it will lead to disease. Therefore, research and new reports on the structure of GPCR have emerged in recent years. More than 30% of the drugs on the market currently use GPCR as a target. However, in such a hot research area, researchers are still aware of the transmembrane domain of a GPCR, a Friction-receptor associated with a variety of human diseases, including cancer, so that the region There is also no suitable research basis for drug design and the like.

As early as the end of 2013, Xu Fei began to study the curly receptors. The first author of the paper, Yang Shizhen, was her first postdoctoral fellow. He joined Xu Fei's research group around July 2014 and started. Independent research on this topic. For Xu Fei's research group, this is a zero-based study. "For GPCR, our research group already has mature research methods, but for curly receptors, we are looking at the literature to understand its biological functionality. At the beginning, Yang Shizhen did not do any research work before entering the group, but he also wanted to do a challenging subject." Xu Fei said.

After three years of struggle, there is still no choice but to stick to it.

Although the analysis of the structure of the curly receptor is still blank, the competition for research in this field is very hot. Xu Fei told reporters: "I know that at least three or four research groups are also doing research on the structure of curly receptors, including two research groups at Stanford University in the United States, a research group at Cambridge University in the United Kingdom, and they all have some The previous research is the basis, so we will emphasize the speed in the whole research, but we are still worried about being reported by others."

Although the difficulty of the research is sufficiently adequate, by the beginning of 2017, there has been no substantial progress in the three years of scientific research. I have done hundreds of experiments, and the experimental data has been shown. It is possible to get an ideal crystal. However, with the passage of three years, the final post time of the postdoctoral is getting closer and closer. The first author of the thesis, Yang Shizhen, must Make a choice: Is it possible to continue to struggle for one year and still have no income, or choose to give up at this moment?

Liu Yunhua’s two major revisions finally broke through

Finally, Yang Shizhen resisted the pressure and decided to postpone a year later. Fortunately, soon the lab finally heard the good news: Before and after the end of September 2017, the research team sent the first draft of the paper to Nature. “For the first draft, the jury gave some suggestions for revision. We spent about five months and found a new collaborator, adding a lot of functional experiments. By the time of the second draft, though And the first draft has been very different, but the jury believes that we need to add some more content, but compared with the first revision, we have a deeper heart, we also hope that the paper can be more perfect, So it took another three or four months. The questions raised by each of the jury members were answered as much as possible through the experimental data. Finally, three judges were unanimously approved in the third draft, probably on July 10 this year. We received a formal notice of consent to the publication, very excited!" Xu Fei said.

Xu Fei told reporters that the 10 curly receptors are relatively close in structure, and breaking one means that the other nine structures are also likely to be able to break through in a relatively short period of time; in addition, among the 10 curly receptors, Only Frizzled-4 is associated with a familial retinal osmotic lesion (FEVR), which can not be detected early with the naked eye. If you miss the timing of treatment, it may cause blindness and bring lifelong regret to your child and family. The structure of Frizzled-4 may provide new ideas for the treatment of genetic eye diseases commonly found in newborns. Therefore, "whether it is for the work of our own research group or for some other research groups that do curly receptors internationally. Words, this breakthrough is just a starting point, not an end point." Xu Fei said. (Reporter Zhou Yuqi)


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